Related Experiment Video
Updated: May 5, 2026
12:17
An In Vitro Caseum Binding Assay that Predicts Drug Penetration in Tuberculosis Lesions
Published on: May 8, 2017
11.4K
Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis
Srinivasa P S Rao1, Suresh B Lakshminarayana, Ravinder R Kondreddi
1Novartis Institute for Tropical Diseases, Singapore 138670, Singapore.
Science Translational Medicine
|December 6, 2013
Summary
New indolcarboxamide compounds show potent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis (Mtb). These compounds target MmpL3, demonstrating efficacy in mouse models and a promising safety profile for tuberculosis treatment.
Area of Science:
- Medicinal Chemistry
- Microbiology
- Pharmacology
Background:
- Drug resistance in tuberculosis (TB) necessitates novel chemotherapeutic agents.
- Multidrug-resistant Mycobacterium tuberculosis (Mtb) poses a significant global health threat.
Purpose of the Study:
- To identify and characterize novel antitubercular agents.
- To evaluate the efficacy and safety of indolcarboxamides against Mtb.
Main Methods:
- Genetic and lipid profiling to identify molecular targets.
- In vitro activity testing against drug-sensitive and resistant Mtb strains.
- In vivo efficacy studies in mouse models and toxicology assessments in rats.
Main Results:
- Indolcarboxamides identified as a new class of bactericidal agents.
- MmpL3 identified as the molecular target, crucial for cell wall biosynthesis.
- Lead candidates NITD-304 and NITD-349 showed potent activity and promising pharmacokinetic profiles.
- Efficacious in treating acute and chronic Mtb infections in mice with a good safety margin in rats.
- No inhibition of major cytochrome P-450 enzymes or the hERG channel.
Conclusions:
- Indolcarboxamides, specifically NITD-304 and NITD-349, are promising candidates for treating multidrug-resistant TB.
- Further development is warranted for these novel antitubercular agents.
Related Concept Videos
01:28Pulmonary Tuberculosis V
1.0K
Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
1.0K
01:31Pulmonary Tuberculosis III
1.8K
Tuberculosis (TB) is a contagious infection primarily affecting the lung parenchyma but which can also affect other body parts. TB can be classified based on disease development, presentation, and the affected anatomical site.
The first classification is based on the development of the disease, and it includes the following categories:
The first classification is based on the development of the disease, and it includes the following categories:
1.8K
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
755
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
755
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
692
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
692
01:29Drugs for Treatment of Ulcerative Colitis in IBD
705
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
705
01:17Drugs for Treatment of Diarrhea-Predominant IBS
1.0K
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
1.0K